The ultimate goal of this proposal is to facilitate the transition of Dr. Thomas Stalnaker into an independent and successful faculty member in the field of addiction research. Dr. Stalnaker has been a post-doctoral fellow for 3+ years under the auspices of the Chemosensory Training Grant at University of Maryland School of Medicine. He has completed a number of studies devoted to understanding the effect of non-contingent cocaine exposure on cognitive function and neural encoding in an odor-guided decision-making task in rats. The career development plan in this proposal will allow Dr. Stalnaker to develop two new technical skills and several professional skills, under the mentorship of Drs. Geoffrey Schoenbaum and Patricio O'Donnell. Most notably, the technical skills include expertise in using intravenous self-administration procedures, and expertise in extracellularly recording and distinguishing midbrain dopamine neurons in awake behaving rats. The research project under this proposal is designed to test the hypothesis, arising from Dr. Stalnaker's work that is described in the Preliminary Studies, that decision-making deficits in addiction result from impairments in signaling outcome-expectancies in orbitofrontal cortex (OFC). Outcome-expectancies are representations of the consequences that can be anticipated to arise from a given situation. The first Specific Aim will test whether brain regions downstream of OFC are impaired in using outcome-expectancies in decision-making in cocaine-experienced rats. In particular, Aim 1 we will test whether inflexible encoding in basolateral amygdala contributes to decision-making deficits in cocaine-experienced rats, and whether the error signal encoded by midbrain dopamine neurons is impaired in an over-expectation task in such rats. The second Specific Aim will directly test whether cocaine-experienced rats are able to use and represent in OFC information about outcome-expectancies. PUBLIC HEALTH RELEVANCE: Addiction is one of the most prevalent social problems in the United States today. The defining impairment in addiction is poor decision-making, which persists well into abstinence both in drug-associated contexts and in everyday decisions. This proposal will contribute to an understanding of the basis of this problem by investigating how cocaine experience disrupts information processing in the brain. [unreadable] [unreadable] [unreadable]